Stereotatic radiosurgery (SRS) is the use of large, precisely directed fractions of radiation to treat tumors in the brain. Techniques for SRS vary substantially and the reduced radiobiological effect from increases in the overall treatment delivery times have been reported in both in vitro and in vivo systems. The reduced effect of the prolonged irradiation schemes is most likely due to incomplete repair mechanisms occurring during intervals in the radiation dose delivery. Studies on time-dose relationship for prolonged radiation exposures during SRS have been limited, and this investigation is needed to provide an accurate radiobiologic/dosimetric model for analysis of clinical outcomes. Results from preliminary studies yielded 2- to 3-fold increases for in vitro cell survival with prolonged irradiation and substantial reduction in tumor response with prolonged in vivo irradiation of tumors in mice. These studies indicate that protracted intermittent SRS treatment schemes are not necessarily biologically isoeffective. This project will utilize human malignant glioma (MG) cell lines with continuous and prolonged radiation delivery schemes using 6 MV x-rays at a constant dose rate to generate in vitro tumor alpha/beta ratios and a family of survival curves. Two MG cell lines from the in vitro studies will be implanted in nude mice to derive correction factors for single vs. prolonged irradiation by clonogenic assay of the in vivo irradiated tumors. The goal of this study is to develop a model of radiobiological response for the overall effect of prolonged SRS treatment delivery that can predict the reduced radiation effect of increased treatment time and provide an isoeffective correction factor.